Ces dernières années, les matériaux à transition de spin (TS) ont suscité un intérêt marqué en raison de leurs applications potentielles, notamment en tant que capteurs ou dispositifs électroniques; typiquement, ces complexes présentent - via un stimulus externe (ex. : température, rayonnement) - une transition de spin réversible "Haut Spin (HS)  Bas Spin (BS)". Dans ce contexte, le travail présenté a porté sur la conception et les études magnétostructuralesde monocristaux de nouveaux systèmes FeII à TS à base de ligands 4-R-1,2,4-triazole comprenant un espaceur alkyl, en combinaison avec soit (i) des entités tétracyanométallates inorganiques ([M(CN)4]2-, M = NiII, PtII, PdII) ou (ii) des cyanocarbanions organiques spécifiques ((tcnsR')-: anions 1,1,3,3-tétracyano-2 thioalkylpropénide) - et ce afin de comprendre in fine l'origine physico-chimique de la forte coopérativité dans ces matériaux remarquables, mais aussi de rationaliser le contrôle et l’optimisation des propriétés de TS. Dans un premier temps, un nouveau sel de polymère 1D [Fe(bntrz)3][Pt(CN)4].H2O (1) - présentant une TS abrupte et une résilience exceptionnelle lors de cycles répétés de commutation - a été synthétisé; les études structurales fines - réalisées sur monocristaux - des états HS et BS ont clairement révélé l'impact des interactions à longue distance sur les propriétés de la TS dans ce système. Ensuite, la substitution de l'anion « rigide » tétracyanométallate ([Pt(CN)4]2-) par l'entité plus « flexible » (tcnset)- nous a conduit au premier exemple de complexe neutre trinucléaire à base de triazole [Fe3(bntrz)6(tcnset)6] (2) présentant une TS complète en une seule étape au-dessus de la température ambiante. La variation systématique du substituant R' de l'anion fonctionnalisé(tcnsR')- a permis l’obtention de deux nouveaux systèmes à TS, à savoir le complexe trinucléaire neutre [Fe3 (bntrz)6(tcnspr)6] (3) et le dérivé 1D [Fe3(bntrz)8(tcnsme)4].(tcnsme)2,4H2O (4), avec des caractéristiques structurales et des comportements de TS distincts. Enfin, dans le but d'évaluer précisément l'impact de différents substituants en 4ème position sur le ligand 1,2,4-triazole, deux nouveaux matériaux 3D basés sur le triazole 2-(3-(4H-l,2,4-triazol-4-yl)propyl)isoindoline-1,3-dione (phtptrz) - i.e. {Fe3(μ2-phtptrz)6[μ2-Pt(CN)4]3}.C2H5OH,5.5H2O (5) et {Fe(phtptrz)[Pt(CN)4].H2O} (6) - ont été synthétisés et caractérisés; une TS en deux étapes est observée pour le composé 5, tandis que le dérivé 6 exprime un comportement paramagnétique caractéristique de l’état de spin S = 2. / In recent years, the spin-crossover (SCO) materials have attracted much interest because of their potential applications such as sensors or electronic displays; these complexes typically exhibit - via an external disturbance (e.g. temperature, radiation) - a reversible “High Spin (HS) Low Spin (LS)” spin transition. In this context, the present work has focused on the design and the magneto-structural investigations of single crystals of novel FeII SCO systems based on 4-R-1,2,4-triazole ligands including an alkyl spacer - with either (i) inorganic tetracyanometallates ([M(CN)4]2-, M = NiII, PtII, PdII) or (ii) specific organic cyanocarbanions ((tcnsR’)-: 1,1,3,3-tetracyano-2-thioalkylpropenide anions) - in order to ultimately understand the physicochemical origin of the strong cooperativity in such striking materials, but also to rationalize the tuning of the SCO properties. At first, a new 1D polymer [Fe(bntrz)3][Pt(CN)4].H2O (1) salt - exhibiting an abrupt spin transition and an exceptional resilience upon repeated switching - has been synthesized; the accurate single crystal investigations of both HS and LS states of the latter clearly revealed the impact of the longrange interactions on SCO properties in this system. Then, the substitution of the ‘rigid’ [Pt(CN)4]2- tetracyanometallate anion by the more ‘flexible’ (tcnset)- entity lead us to the first example of triazole-based SCO FeII trinuclear neutral complex [Fe3(bntrz)6(tcnset)6] (2) exhibiting a complete one-step spin transition above room temperature. The systematic variation of the R’ substituent from the functionalized (tcnsR’)- anion resulted in two new FeII SCO systems, i.e. the neutral trinuclear complex [Fe3(bntrz)6(tcnspr)6] (3) and the 1D [Fe3(bntrz)8(tcnsme)4](tcnsme)2.4H2O (4) derivative, with distinct structural characteristics and SCO behaviours. Finally, with the purpose to further evaluate the impact of different substituents at the 4th position onto 1,2,4-triazole ligand, two new 3D materials based on the functionalised triazole 2-(3-(4H-1,2,4-triazol-4-yl)propyl)isoindoline-1,3-dione (phtptrz) - {Fe3(μ2-phtptrz)6[μ2-Pt(CN)4]3}.C2H5OH,5.5H2O (5) and {Fe(phtptrz)[Pt(CN)4].H2O} (6) - have been synthesized and characterized; a two-step SCO behaviour is observed only in 5, while 6 shows a characteristic paramagnetic behavior.

No description available.

La diffraction des rayons X permet d’obtenir des informations sur la structure atomique et même sur la distribution de charges de composés sous forme cristalline, ce qui est d’une importance fondamentale pour la compréhension de leurs propriétés. Accéder expérimentalement à une description de la distribution de charges de systèmes macromoléculaires reste rarement possible malgré les améliorations techniques. Pour pallier cette limite, la transférabilité des paramètres de distributions de charges est un moyen fiable d’obtenir pour ces systèmes un modèle estimé et d’en déduire leurs propriétés électrostatiques. Les résultats présentés dans ce travail de thèse s’intègrent dans une dynamique visant à étendre les méthodes initialement réservées pour l’étude des petites molécules aux systèmes macromoléculaires. Il s’articule autour du développement de la suite de logiciels MoPro et de la banque de données ELMAM (Experimental Library of Multipolar Atom Model) pour l’étude des énergies des interactions électrostatiques au sein du site actif de complexes enzyme-inhibiteur. L’étude du fidarestat, un inhibiteur de l’holoenzyme aldose réductase, réalisée à partir de données obtenues à très haute résolution, est exposée dans ce manuscrit et a servi notamment à l’amélioration de la banque ELMAM en vue de l’étude des complexes holoenzymes aldo-keto réductase. A cette occasion, la légitimité du recours aux modèles transférés de distribution de charges a été discutée pour la première fois par une estimation statistique des incertitudes sur les énergies d’interaction électrostatique entre enzyme et inhibiteur / X-ray diffraction allows to obtain information about atomic structure and charge density distribution of crystal-state compounds, which is of main interest for the understanding of their properties. Reaching experimentally charge density distribution description of macromolecular systems is rarely possible despite technical improvements. To get around this limit, the transferability of charge density distribution parameters is a reliable way to obtain for these systems estimated model and to deduce their electrostatic properties. Works introduced in this PhD thesis manuscript take part in the will of extending methods initially for study of small molecules to macromolecular systems. It is centered on the development of the MoPro software suite and of ELMAM database (Experimental Library of Multipolar Atom Model) for the study of electrostatic interaction energies in enzyme-inhibitor complexes’ active site. The study of fidarestat, an inhibitor of aldose reductase holoenzyme, performed using ultra-high resolution data, is exposed in this manuscript and allowed to improve ELMAM database for the study of electrostatic interaction in aldo-keto reductase holoenzyme complexes. Moreover, the legitimacy of using transferred charge density distribution models was discussed for the first time, thanks to statistical estimation of uncertainties on electrostatic interaction energies between enzyme and inhibitor

<div><div>In the forensic science community, there is a vast need for tools to help assist investigations when standard DNA profiling methods are uninformative. Methods such as Forensic DNA Phenotyping (FDP) and proteomics aims to help this problem and provide aid in investigations when other methods have been exhausted. FDP is useful by providing physical appearance information, while proteomics allows for the examination of difficult samples, such as hair, to infer human identity and ancestry. To create a “biological eye witness” or develop informative probability of identity match statistics through proteomically inferred genetic profiles, it is necessary to constantly strive to improve these methods. </div><div><br></div><div>Currently, two developmentally validated FDP prediction assays, ‘HIrisPlex’ and ‘HIrisplex-S’, are used on the capillary electrophoresis to develop a phenotypic prediction for eye, hair, and skin color based on 41 variants. Although highly useful, these assays are limited in their ability when used on the CE due to a 25 variant per assay cap. To overcome these limitations and expand the capacities of FDP, we successfully designed and validated a massive parallel sequencing (MPS) assay for use on both the ThermoFisher Scientific Ion Torrent and Illumina MiSeq systems that incorporates all HIrisPlex-S variants into one sensitive assay. With the migration of this assay to an MPS platform, we were able to create a semi-automated pipeline to extract SNP-specific sequencing data that can then be easily uploaded to the freely accessible online phenotypic prediction tool (found at https://hirisplex.erasmusmc.nl) and a mixture deconvolution tool with built-in read count thresholds. Based on sequencing reads counts, this tool can be used to assist in the separation of difficult two-person mixture samples and outline the confidence in each genotype call.<br></div><div><br></div><div>In addition to FDP, proteomic methods, specifically in hair protein analysis, opens doors and possibilities for forensic investigations when standard DNA profiling methods come up short. Here, we analyzed 233 genetically variant peptides (GVPs) within hair-associated proteins and genes for 66 individuals. We assessed the proteomic methods ability to accurately infer and detect genotypes at each of the 233 SNPs and generated statistics for the probability of identity (PID). Of these markers, 32 passed all quality control and population genetics criteria and displayed an average PID of 3.58 x 10-4. A population genetics assessment was also conducted to identify any SNP that could be used to infer ancestry and/or identity. Providing this information is valuable for the future use of this set of markers for human identification in forensic science settings. </div></div><div><br></div>

No description available.

Thin-film organic field effect transistors (OFETs) have attracted growing interest in recent years due to their promising electrical, optical and mechanical properties. Especially, oligothiophenes and their derivates are candidates with good prospects for application as the organic semiconducting material in such devices. They possess an extended, polarisable aromatic π-electron system that promotes a high structural arrangement of the molecules. The charge transport in the organic film is realised in the direction perpendicular to the plane of the thiophene rings via a hopping transport mechanism. Thus, a good π-π-overlap and a consequent stacking of the thiophene molecules in the film perpendicular to the gate substrate is essential to achieve excellent electric properties such as high charge carrier mobilities and low resistive losses. The highly polarisable thiophene-based molecules are also very attractive materials that are potentially applicable as the field-sensitive organic semiconducting component of a ferroelectric OFET device. In such a device, the dielectric gate element of a conventional OFET setup is substituted by a ferroelectric substrate. The electric field that is induced by the polarisation of the ferroelectric material serves as gate field and controlls the charge injection and charge density inside the device. In this thesis, thiophene-based molecules are investigated in detail with respect to their application as field-sensitive organic semiconducting component in a ferroelectric OFET device employing quantum-chemical ab initio and DFT-based methods. We demonstrate that the phosphonic acids can bind the organic molecules to the dielectric or ferroelectric material and well-anchored, robust self-assembled monolayers are formed. Furthermore, special focus is put on the influence of the intermolecular interactions among the organic molecules on the technologically relevant structural and electronic properties. It is found that the CN···HC hydrogen bond link the molecules into extended ribbons, but the π-π-stacking-stacking interaction is the main driving force in the self-assembly of the molecules. We also establish in detail the influence of the electric field on the phosphonic acid anchoring molecule and some quarterthiophene derivates. For the latter, the strongest field-sensitivity is obtained for an external electric field aligned parallel to the extension of the thiophene framework. Hence, they are suitable to act as the field-sensitive organic components in devices that take advantage of a band-gap engineering. Moreover, the present results emphasise the importance of the adsorption morphology of the molecules in the film in a π-stacked fashion with their longitudinal axis oriented parallel to the (orthonormal) electric field induced by the ferroelectric substrate.

The sensitivity, speed, and reproducibility of modern mass spectrometers enable in-depth new functional looks into the cellular proteome. Thousands of proteins can be detected in a single sample. In Co-Fractionation Mass Spectrometry (CF-MS) method, the input sample is fractionated by any biochemical method of choice. The reduced complexity of each fractionated sample leads to better proteome coverage. The separation profiles provide functional information on the proteins. This application has been used to predict organelle localization based on co-purification with marker proteins. More recently, CF-MS is being used to measure the apparent masses and determine the localization of soluble or membrane-associated protein complexes. This Ph.D. dissertation focuses on the extension of the boundary of CF-MS application to learn how protein complex evolution and protein complex composition have been accomplished. In the first part of this dissertation, the data will be presented on the degree to which variation in protein oligomerization across plant species is present, how proteomics in phylogenetic analysis (phyloproteomics/evolutionary proteomics) helps understand the evolutionary changes, and how oligomerization drives neofunctionalization during plant evolution. The latter part will describe that CF-MS coupled with multiple orthogonal chromatographic separations increases the resolving power of the profiling technique, enabling the composition of protein complexes to be predicted in the subaleurone layers of rice endosperm. Lots of novel protein complexes involved in RNA binding protein, translation, and the tissue-species metabolism will be discussed.

<p>Home cage aggression in male laboratory mice continues to challenge preclinical researchers. It reduces animal welfare and can alter research parameters, potentially reducing the validity and reliability of study data. While simply reducing aggression would be beneficial, promoting socio-positive, affiliative behaviors would greatly improve mouse welfare as mice are a social species. Mice also use olfaction to communicate, so this sensory modality could be used as a tool to improve social interactions in the home cage. A scoping review of the literature on how mammalian odor signals impact same sex social behavior found that studies are dominated by rodent subjects, treatments from urine, and aggression measures (Chapter 1). As a whole, urine treatments had a variable effect on aggression. This review highlights that treatments from non-urinary sources are not often tested, and affiliative behavior is rarely measured.</p> <p>One murine odor source worth exploring is found in used nesting material. Mice build complex nests for insulation and it has been speculated that the nest holds odor signals that appease home cage aggression, particularly aggression triggered by cage cleaning. It has been suggested that the nest contains secretions from plantar sweat glands, but the chemical content of neither nesting material nor plantar sweat have been examined. The main goals of this dissertation are to identify the odors stored in used nesting material, determine the sources of those odors, and test them for a behavioral role.</p> <p>Samples of used nesting material were collected from cages of group housed male mice. Further, plantar sweat, saliva, and urine were collected from the dominant and subordinate mouse in each cage as plausible odor sources. All samples were analyzed for protein and volatile organic compound content. Home cage aggression and affiliative behavior were also recorded to compare to odor profiles. Protein profiles showed that used nesting material contains a variety of proteins that primarily originate from plantar sweat, saliva, and urine sources (Chapter 2). A large proportion of these proteins contain messages about individual identity and bind volatile compounds that further contribute to identity cues. This suggests that the nest aids in maintaining a familiar odor environment. Analysis of volatile content showed that small compounds in the nest are also traced back to plantar sweat, saliva, and urine sources (Chapter 3). Few of the compounds have a known behavior role. However, one compound detected in nest, sweat, and saliva samples had a negative correlation with home cage aggression and three compounds (two from sweat and one from urine) had a positive correlation with affiliative behaviors, making them potential candidates for controlled studies on social behavior.</p> <p>Before testing the four candidate compounds, a challenge from the correlation study needed to be addressed. Body fluid samples were collected from individual mice based on social status, as this factor impacts production of known murine pheromones. Further, aggression is typically directed from a dominant to a subordinate mouse for territorial reasons. An aggression appeasement signal is likely to be produced by a subordinate to mitigate the dominant mouse’s perceived threat. Data from the correlation study showed no odor profile differences based on social status, and the pheromones that are known to vary with social status did not differ between dominant and subordinate mice. Therefore, Chapter 4 assesses the convergent validity of several dominance measures. Over one week, home cage interactions were observed in group housed male mice. For every aggression occurrence, the aggressor and target mouse was recorded to calculate individual dominance rankings in each cage. Then, individual mice were evaluated for the following measures known to correlate with dominance: levels of urinary darcin (a murine pheromone); scores from three rounds of the tube test; and ratio of preputial gland weight to body length. Postmortem wounding was also compared. Results showed that urinary darcin and preputial gland ratio have strong convergent validity with dominance ranking based on home cage aggression.</p> <p>Finally, the four candidate compounds (identified in Chapter 3) were developed into treatment solutions to assess their effect on home cage social behavior (Chapter 5). Cages of group housed male mice were randomly assigned one of five treatments (four compounds + control) and home cage aggression and affiliative behavior were recorded for one week. Postmortem wounding was recorded as a secondary aggression measure and social stress was measured through fecal corticosterone metabolites from each cage’s dominant and subordinate mouse (rank based on preputial gland ratio). Treatment did not predict changes in most measures. This may be due to limitations in application or from the original correlation study, which are further discussed.</p> <p>Although the final study showed null results, future research is still warranted to fine tune application methods and gain a better understanding of how odor signals impact interactions other than aggression. The relationship between olfaction and affiliative behaviors is largely unexamined and this dissertation is a first step in filling that gap.</p>

Methods of slab-geometry molecular dynamics computer simulation were tested, compared, and applied to the prediction of activity coefficients, interfacial electrochemistry characterization, and ion transport through a model biological channel-membrane structure. The charged-sheets, 2-D Ewald, corrected 3-D Ewald, and corrected particle-particle-particle-mesh (P3M) methods were compared for efficiency and applicability to slab-geometry electrolyte systems with discrete water molecules. The P3M method was preferred for long-range force calculation in the problems of interest and was used throughout. The osmotic molecular dynamics method (OMD) was applied to the prediction of liquid mixture activity coefficients for six binary systems: methanol/n-hexane, n-hexane/n-pentane, methanol/water, chloroform/acetone, n-hexane/chloroform, methanol/ chloroform. OMD requires the establishment of chemical potential equilibrium across a semi-permeable membrane that divides the simulation cell between a pure solvent chamber and a chamber containing a mixture of solvent and solute molecules in order to predict the permeable component activity coefficient at the mixture side composition according to a thermodynamic identity. Chemical potential equilibrium is expedited by periodic adjustment of the mixture side chamber volume in response to the observed solvent flux. The method was validated and shown to be able to predict activity coefficients within the limitations of the simple models used. The electrochemical double layer characteristics for a simple electrolyte with discrete water molecules near a charged electrode were examined as a function of ion concentration, electrode charge, and ion size. The fluid structure and charge buildup near the electrode, the voltage drop across the double layer, and the double layer capacitance were studied and were found to be in reasonable agreement with experimental findings. Applied voltage non-equilibrium molecular dynamics was used to calculate the current-voltage relationship for a model biological pore. Ten 10-nanosecond trajectories were computed in each of 10 different conditions of concentration and applied voltage. The channel-membrane structure was bathed in electrolyte including discrete water molecules so that solvation, entry, and exit effects could be studied. Fluid structure, ion dynamics, channel selectivity, and potential gradients were examined. This work represents the first such channel study that does not neglect the vital contributions of discrete water molecules.

No description available.